Membrane-bound protein kinase A inhibits smooth muscle cell proliferation in vitro and in vivo by amplifying cAMP-protein kinase A signals
| Autor: | Antonio Feliciello, Adriana Gallo, Massimo Chiariello, Giancarlo Troncone, E. V. Avvedimento, Ciro Indolfi, Luigi Cavuto, Daniele Torella, Giovanna Allevato, Carmela Coppola, Eugenio Stabile, Emilio Di Lorenzo, Cinzia Perrino |
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| Přispěvatelé: | Indolfi, C., Stabile, Eugenio, C., Coppola, A., Gallo, Perrino, Cinzia, G., Allevato, L., Cavuto, D., Torella, E. D., Lorenzo, Troncone, Giancarlo, A., Feliciello, Avvedimento, VITTORIO ENRICO, M., Chiariello, Indolfi, C, Coppola, C, Gallo, A, Allevato, G, Cavuto, L, Torella, D, Di Lorenzo, E, Feliciello, Antonio, Chiariello, M. |
| Rok vydání: | 2001 |
| Předmět: |
Time Factors
Physiology genetics Rats Rat drug effects Time Factors Tumor Suppressor Proteins Tunica Intima drug effects/physiology Cell 8-Bromo Cyclic Adenosine Monophosphate A Kinase Anchor Proteins Cell Cycle Proteins Mitogen-activated protein kinase kinase Muscle Smooth Vascular chemistry/pathology Tunica Media PKA Cells Cultured Neointimal hyperplasia Kinase Recombinant DNA Gene Transfer Techniques biosynthesis/drug effects Gene Transfer Techniques Immunohistochemistry Microtubule-Associated Protein Immunohistochemistry Cell biology Carotid Arteries chemistry/pathology Smooth Cardiology and Cardiovascular Medicine Tunica Media Microtubule-Associated Proteins Cell Division Cyclin-Dependent Kinase Inhibitor p27 Signal Transducing Animals Carotid Arterie Cultured Chloramphenicol O-Acetyltransferase Plasmids Signal Transduction Chloramphenicol O-Acetyltransferase medicine.medical_specialty drug effects/genetics/metabolism Signal Transduction drug effects/metabolism Cyclin-Dependent Kinase Inhibitor p27 DNA Recombinant Fusion Proteins DNA Recombinant Biology AKAP drug effects/genetics/metabolism Cyclic AMP-Dependent Protein Kinase In vivo muscle cell proliferation Internal medicine Vascular medicine Animals Rats Wistar Protein kinase A Adaptor Proteins Signal Transducing analysis Muscle Cell growth pharmacology A Kinase Anchor Proteins Adaptor Protein Tumor Suppressor Proteins genetics/metabolism Cell Cycle Proteins Cell Division DNA medicine.disease Cyclic AMP-Dependent Protein Kinases In vitro cytology/drug effects/metabolism Plasmid Rats Endocrinology Wistar Recombinant Fusion Protein Carrier Proteins Tunica Intima chemistry/pathology Carrier Protein |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1524-4571 |
| Popis: | Abstract —cAMP-dependent protein kinase is anchored to discrete cellular compartments by a family of proteins, the A-kinase anchor proteins (AKAPs). We have investigated in vivo and in vitro the biological effects of the expression of a prototypic member of the family, AKAP75, on smooth muscle cells. In vitro expression of AKAP75 in smooth muscle cells stimulated cAMP-induced transcription, increased the levels of the cyclin-dependent kinase-2 inhibitor p27 kip1 , and reduced cell proliferation. In vivo expression of exogenous AKAP75 in common carotid arteries, subjected to balloon injury, significantly increased the levels of p27 kip1 and inhibited neointimal hyperplasia. Both the effects in smooth muscle cells in vitro and in carotid arteries in vivo were specifically dependent on the amplification of cAMP-dependent protein kinase (PKA) signals by membrane-bound PKA, as indicated by selective loss of the AKAP75 biological effects in mutants defective in the PKA anchor domain or by suppression of AKAP effects by the PKA-specific protein kinase inhibitor. These data indicate that AKAP proteins selectively amplify cAMP-PKA signaling in vitro and in vivo and suggest a possible target for the inhibition of the neointimal hyperplasia after vascular injury. |
| Databáze: | OpenAIRE |
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